Pulmonary emphysema and interstitial pneumonia are two diffuse lung diseases which may be viewed as responses of the lung to injury. One of the identifying features of emphysema is the specific alteration of the elastic tissue network, whereas in interstitial pneumonia, widespread involvement of many of the elements of the pulmonary parenchyma occurs. Understanding the nature of these processes has been limited in early stages of disease. We propose to study animal models of emphysema and diffuse interstitial pneumonia in a concerted attempt to gain insights into the pathophysiological and patho-biochemical changes which takes place in these progressing lesions. Lung mechanics and gas exchange will be examined. Connective tissue biochemistry, prostaglandins, catecholamines and cyclic nucleotides will be evaluated, and the full range of ultrastructural techniques will be applied to the various lesions. Modified elastases will be synthesized to study in these animal models. Studies on pure cell systems from lung will provide additional insights. In parallel studies, an assessment of lung growth and development in normal and pneumonectomized animals will be carried out employing many of the same physiologic, biochemical and ultrastructural techniques. Radioautography at the light and electron microscopic level are an integral part of all animal studies. The possible role of cell mediated immunity in the pathogenesis of these diseases will be investigated. A laboratory devoted to clinical epidemiological studies will interrelate with several of the medical science disciplines represented in the program. It is anticipated that the results of all these studies will give rise to greater understanding of processes of normal lung growth and the nature of the injuries and their repair which results in the development of pulmonary emphysema and chronic interstitial pneumonia. New diagnostic and therapeutic techniques may well derive from these studies.